Nobuyuki Takai

The simple indicator for revascularization of acute middle cerebral artery occlusion using angiogram and ultra-early embolectomy

BACKGROUND The purpose of the study was: (1) to find a clinical indicator for revascularization of acute middle cerebral artery (MCA) occlusion using angiograms of 100 patients examined immediately after onset and treated medically and (2) to investigate 10 ultra-early MCA embolectomies. METHODS Quantity of collateral circulation, based on time required for conduction of contrast media to the insular portion of the MCA from the anterior cerebral artery, MCA conduction time (MCT) was graded as: Grade 1: In the arterial phase, there was conduction not only to the insular portion of the MCA but also to proximal M2; Grade 2: Conduction to the insular portion was present in late arterial phase; Grade 3: Conduction was present in capillary phase; Grade 4: Conduction was present in venous phase; Grade 5: No conduction was seen. The results of embolectomy are discussed. RESULTS MCT can predict the extent of resultant low-density area on computed tomographic scan. For Grades 3, 4, or 5, embolectomy could be considered superior to medical treatment, if the low-density area was localized in the basal ganglia or centrum semiovale after surgery. Consequently, embolectomy was effective in four cases recanalized within 6 hours of onset. Except for one Grade 5 case, the remaining nine cases showed neither lethal hemorrhagic infarction nor brain edema. Overall outcome was significantly better than cases treated medically (p < 0.05), but some cases did not recover from hemiparesis due to infarcts in the area of the lenticulostriate arteries. CONCLUSIONS MCT helps to predict the applicability of revascularization of acute MCA occlusion. Efficacy of embolectomy depends on revascularization within 6 hours of onset. Even after complete MCA flow restoration, infarcts in the area of the lenticulostriate arteries cannot always be prevented.

Effects of Cytokines on Cultured Microvascular Endothelial Cells Derived from Gerbil Brain

Microvascular endothelial cells were isolated from gerbil brain and cultured. These cells retained an endothelial-specific marker, FVIII-related antigen. Alkaline phosphatase activity was also present in early passage. Two weeks after plating, these cells were attached to the culture dishes and had become like cobblestones in appearance. Then, the addition of tumor necrosis factor at a concentration of 1000 U/ml or more suppressed the DNA synthesis activity of endothelial cells by about 70% and induced morphological changes in the cells, which developed a spindle-like form and showed overlapping of cells, indicating loss of contact inhibition. The administration of interferon-tau induced no change. When a similar experiment was performed using culture supernatants of human glioma cells that had been cultured for a few days, DNA synthesis activity was suppressed by approximately 50% or more in 6 of 12 samples. The suppression of activity, however, was abolished by the addition of anti-tumor necrosis factor antibody in these 6 cases, suggesting the presence of activity resembling that of the tumor necrosis factor in the culture supernatants.

Functional analysis of interleukin-2 in immune surveillance against brain tumors

We studied the capacity of peripheral blood lymphocytes (PBLs) from patients with malignant brain tumors to produce interleukin-2 (IL-2) and to respond to IL-2. The role of IL-2 in the generation of T cells cytotoxic against tumor cells was also studied. PBLs from the patients with malignant brain tumors tended to produce a level of IL-2 lower than that in normal controls because of the decreased number of IL-2-producing T cells. Phytohemagglutinin activated PBLs from normal controls and the patients, however, responded equally well to IL-2. This indicates that the expression of IL-2 receptors is abundant in PBLs of these patients, although IL-2 production may be depressed. Furthermore, after incubation with IL-2, PBLs from the patients with malignant glioma exhibited higher natural killer activity and strong cytotoxicity against glioma cells. This increased cytotoxicity was evident by Day 3 of culture in IL-2 and remained effective for at least 2 days. These observations of antitumor cytotoxicity make IL-2 a likely candidate for use in adoptive immunotherapy.