A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state.

An animal model involving stepwise occlusion of the common carotid arteries (sCCAO) in DBA/2 mice is presented in which the right and left carotid arteries were permanently ligated within a time interval of four weeks. Thereafter, cerebral functional and structural parameters were determined at acute (15 min) and subchronic (1 day; 3, 7, and 14 days) time points after sCCAO. Quantitative changes in regional cerebral blood flow (rCBF) as determined by the [14C]iodoantipyrine method, energy state (ATP, phosphocreatine, ADP, AMP, adenosine) as shown by HPLC, brain histopathology, and neuronal densities were measured in both hemispheres. Acute sCCAO was accompanied by a drastic reduction in cerebral energy-rich phosphate concentrations, ATP and phosphocreatine, and in rCBF of more than 50%. In contrast, cortical adenosine increased around five-fold. Subchronic sCCAO, however, was associated with normalization in brain energy metabolites and near-complete restoration of rCBF, except in the caudate nucleus (-40%). No marked signs of necrotic or apoptotic cell destruction were detected. Thus, during the subchronic period, compensatory mechanisms are induced to counteract the drastic changes seen after acute vessel occlusion. In conclusion, this sCCAO mouse model may be useful for long-lasting investigations of stepwise deterioration contributing to chronic cerebrovascular disorders.

Juxtaposition of an epidural intraforaminal cavernous hemangioma and an intradural schwannoma.

STUDY DESIGN: A case of juxtaposition of a purely extradural cavernous hemangioma and an intradural schwannoma in the thoracic spine is reported. OBJECTIVES: The objectives of this study were to present a rare and before-surgery unexpected combination of spinal tumors, which may complicate surgical removal; and to discuss the radiologic features and the possible pathogenesis of this combination of tumors and its implications on surgical therapy. SUMMARY OF BACKGROUND DATA: Juxtaposition of different spinal tumors is exceedingly rare in patients without neurofibromatosis. To the authors' knowledge, no combination of a purely epidural spinal cavernous hemangioma with an intradural schwannoma has been previously reported. MATERIAL AND METHODS: A 47-year-old woman presented with progressive paraparesis. Magnetic resonance imaging revealed a partly cystic intradural mass at the T6-T7 level and a solid extradural intraforaminal component that demonstrated slightly different signal characteristics. An intra-/extradural schwannoma was assumed. RESULTS: Surgical exposure displayed a highly vascularized lobulated mass within the left neuroforamen at T6-T7. There was no continuity with the larger intradural, cystic, and mildly vascularized lesion. Histologic examination diagnosed an extradural cavernous hemangioma and an intradural schwannoma. CONCLUSIONS: The segmental juxtaposition of lesions should be considered in the differential diagnosis of spinal pathology.

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.