Kimiko Umemura

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Background and Purpose— Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. Methods— Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. Results— Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P<0.05) lower in transgenic mice (1.30±0.72, 1.12±0.04, and 14.0±7.7%, respectively) than in wild-type mice (2.56±0.93, 1.23±0.12, and 31.9±9.7%, respectively). Percentages of apoptotic cells were also significantly (P<0.001) lower in transgenic mice (cortex, 5.2±3.3%; hippocampus, 3.4±7.0%) than in wild-type mice (cortex, 41.1±16.9%; hippocampus, 58.9±15.3%). Conclusions— These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.

Specific Shrinkage of Carotid Forks in Moyamoya Disease: A Novel Key Finding for Diagnosis

This study was aimed to analyze the outer diameter of the involved arteries in moyamoya disease, using three-dimensional (3D) constructive interference in steady state (CISS) and direct surgical inspection. Radiological evaluation was performed in 64 patients with moyamoya disease. As the controls, six patients with severe middle cerebral artery (MCA) stenosis and 17 healthy subjects were also recruited. On 3D-CISS, the outer diameter was quantified in the supraclinoid portion of internal carotid artery (C1), the horizontal portions of MCA (M1) and anterior cerebral artery (A1), and basilar artery. The involved carotid fork was directly observed during surgery in another series of three adult patients with moyamoya disease. In 53 adult patients with moyamoya disease, the outer diameters of C1, M1, and A1 segments were 2.3 ± 0.7 mm, 1.3 ± 0.5 mm, and 1.0 ± 0.4 mm in the involved side (n = 91), being significantly smaller than the control (n = 17), severe M1 stenosis (n = 6), and non-involved side in moyamoya disease (n = 15, P < 0.01). There were significant correlations between Suzuki’s angiographical stage and the outer diameters of C1, M1, and A1 (P < 0.001). The laterality ratio of C1 and M1 was significantly smaller in unilateral moyamoya disease (n = 20) than the controls and severe MCA stenosis (P < 0.01). Direct observations revealed a marked decrease in the outer diameter of the carotid fork (n = 3). These findings strongly suggest specific shrinkage of the involved arteries in moyamoya disease, which may provide essential information to distinguish moyamoya disease from other intracranial arterial stenosis and shed light on the etiology and novel diagnosis cue of moyamoya disease.

Extracranial-intracranial bypass surgery at high magnification using a new high-resolution operating microscope: technical note

BACKGROUND We report a precise technique for EC-IC bypass surgery using a stereoscopic high-resolution microscope at magnifications of 40x and 50x. METHODS A stereoscopic operating microscope (Mitaka MM50 Surgical Microscope; Mitaka Kohoki Co, Tokyo, Japan) was used in STA-MCA anastomosis. This microscope has 2 optical systems, a standard zooming system, a newly developed high-magnification system, and 4 fixed working distances of 200, 250, 300 and 350 mm, with highest magnifications of 50.4x at 200 mm and 40.3x at 250 mm. High resolution is achieved by a new lens design in the optical system, which makes the image of the object very clear at high magnification. The magnification can be changed depending on the circumstances in a given procedure. The STA-MCA anastomoses were performed using this microscope. RESULTS Very small vessels were observable, and arterial anastomosis could be performed precisely at high magnification. All anastomoses were patent on postoperative angiograms. CONCLUSIONS Use of the new microscope allows visualization and manipulation of small vessels at high magnification and high resolution and may be very useful in EC-IC bypass surgery.