The role of DAPK-BimEL pathway in neuronal death induced by oxygen-glucose deprivation.

Death-associated protein kinase (DAPK) has been found promoting cell death under stress conditions, including cell death during brain ischemia. However, little is known about the mechanisms how DAPK is involved in the neuronal death-promoting process during ischemia. The present study was to examine the DAPK signal transduction pathways using an ischemia mimicking model, oxygen glucose deprivation (OGD). OGD was induced by incubating SH-SY5Y neuroblastoma cells in glucose-free culture medium flushed with a mixture of N2 and CO2. DAPK expression was inhibited by transfection of SH-SY5Y cells with DAPK short hairpin RNA (shRNA). Cell death induced by OGD exposure was assessed by Annexin V-FITC and propidium iodide (PI) assay. Protein expressions were examined by Western blot and protein interactions were detected with immunoprecipitation followed by Western blot. OGD treatment resulted in neuronal death and led to DAPK activation as demonstrated by increase of DAPK (active form) and decrease of phospho-DAPK (inactive form). The activation of DAPK in turn led to BimEL up-regulation and endoplasmic reticulum (ER) stress activation. Further analyses showed that DAPK mediated BimEL expression through extracellular signal-regulated protein kinase1/2 (ERK1/2) inactivation and c-Jun-N-terminal kinase1/2 (JNK1/2) activation. These findings revealed novel signal transduction pathways leading to neuronal death in response to OGD.

Rosai-Dorfman disease mimicking parasagittal meningioma: case presentation and review of literature.

BACKGROUND: Sinus histiocytosis with massive lymphadenopathy was originally described by Rosai and Dorfman in 1969. It usually presents with bilateral painless cervical lymphadenopathy. In extremely rare circumstances, the CNS can be affected. Only 21 prior cases of intracranial involvement have been reported. CASE REPORT: A 33-year-old white male presented with a 2-week history of progressive cephalgia. The patient underwent MRI testing that revealed an enhancing mass in the right parasagittal region with associated edema. Preoperative diagnosis was right parasagittal meningioma. The patient underwent craniotomy with complete resection of the mass. Histopathology was compatible with Rosai-Dorfman disease (RDD). CONCLUSION: Rosai-Dorfman disease is rarely found intracranially; however, its ability to mimic meningioma as well as other pathologies underlines its importance. With so few reported cases of intracranial involvement, more experience will be necessary before this clinical presentation and prognosis can be clearly outlined.

Transependymal benign dorsally exophytic brain stem gliomas in childhood: diagnosis and treatment recommendations.

Sixteen children with dorsally exophytic transependymal benign brain stem gliomas were treated at the Hospital for Sick Children, Toronto, between 1949 and 1985. The diagnosis of these benign brain stem gliomas was based on neuroradiographic and operative observations. Five children were diagnosed in the pre-computed tomography (CT) era using ventriculography and pneumoencephalography, and 11 children were diagnosed using CT with and without contrast enhancement. Histological diagnosis was obtained in all 16 cases. In 1980, we first described this distinct group of benign brain stem gliomas, which accounted for 8% (total, 121 cases) of all brain stem gliomas diagnosed at our institution. However, with the use of high resolution CT in recent years, earlier and better definition of this particular type of brain stem tumor can be made. During the 10 years (1976 to 1985) in which CT has been used for preoperative evaluation in our institution, we have treated 49 patients with primary brain stem tumors. Eleven of these cases (22%) fell into the category of dorsally exophytic transependymal benign brain stem tumors. These tumors characteristically protrude into and largely fill the 4th ventricle, breaking through the overlying ependyma and frequently extending into the cisterna magna. On CT, they are isodense and enhance brightly with contrast agent. Clinically, these patients have a longer history of symptoms in comparison with patients with the more malignant, intrinsic types of brain stem tumor. All of our patients were treated by subtotal resection. Radiotherapy was utilized in 7 of the 16 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and management of pediatric brain-stem gliomas.

The authors reviewed the cases of 49 children, ranging in age from 9 months to 15 years, who were diagnosed by computerized tomography (CT) as having brain-stem glioma. Four distinct groups of brain-stem gliomas were identified based on CT scan characteristics: Group I included isodense contrast-enhancing tumors that were dorsally exophytic into the fourth ventricle; Group II(a) included hypodense nonenhancing intrinsic tumors of the brain stem; Group II(b) included intrinsic tumors of the brain stem with hyperdense exophytic components extending ventrally and laterally into the cerebellopontine and prepontine cisterns; Group III included intrinsic cystic tumors with contrast-enhancing capsules; and Group IV included focally intrinsic tumors of the brain stem that were isodense and enhanced brightly on administration of contrast medium. The clinical presentation, efficacy of surgical intervention, pathology, and prognosis of these tumors were correlated within these groupings. Eleven patients had Group I tumors, all of which were surgically resected; 10 of the 11 lesions were proven to be low-grade gliomas. These patients had an excellent prognosis; 10 of the 11 survived, with a mean follow-up period of 4.5 years. There were 18 patients with Group II(a) tumors; although tumor biopsy was attempted on eight of these, pathological diagnosis at the time of surgery was made in only one case. These patients did poorly; the mean survival time was 6.2 months. The seven Group II(b) tumor patients demonstrated a similarly poor prognosis: all of them died within 23 months of diagnosis, with a mean survival time of 12 months. Only two of six patients undergoing biopsy had sufficient tissue for histological verification. Three of the four patients with Group III tumors died; their mean survival time was 11.5 months. Successful histological examination was carried out in all four cases. The nine Group IV tumor patients did reasonably well; seven of these patients remain alive, with a mean follow-up period of 2.3 years. Histological diagnosis was obtained in three of the seven patients who were explored in this group. This classification system has proven to be of value in determining prognosis and efficacy of surgical intervention.

Carbamazepine-induced hemolytic anemia.

A patient who had recently undergone craniotomy for a meningioma experienced carbamazepine (Tegretol)-induced hemolytic anemia. To our knowledge, this is the first reported case of hemolytic anemia clearly induced by carbamazepine.