Hironaka Igarashi

Diffusion-weighted imaging in kainic acid-induced complex partial status epilepticus in dogs.

OBJECTIVEnTo investigate diffusion-weighted imaging (DWI) in status epilepticus, a canine model of kainic acid (KA)-induced complex partial status epilepticus (CPSE) was produced. In order to validate its usefulness, MR imaging was carried out at various times following onset of CPSE followed by histopathology.nnnMATERIAL AND METHODSnSix normal dogs were used in this study. In each dog, a cannula was stereotactically inserted into the left amygdala. One week after surgery, all dogs were imaged at MRI. Pre-injection imaging consisted of T2 weighted (T2W) imaging, fluid attenuated inversion recovery (FLAIR), and DWI. Two weeks after surgery, five dogs received intraamygdaloid KA microinjections. One dog was used as a control. MRI was carried out at 3, 6, 12, 24 and 48 h after onset of CPSE. Animals were euthanized immediately after MRI for histopathological evaluation. The average of each apparent diffusion coefficient (ADC) in the regions of interest was calculated from each DWI.nnnRESULTSnAt 3 and 6 h, DWI hyperintensity and low ADC were found in the injected amygdala, without any T2W and FLAIR imaging changes. At 12 and 24 h, all imaging showed hyperintensity with higher ADC in the amygdala and the hippocampus. At 48 h, all imaging techniques showed continued hyperintensity, but ADC showed a trend towards normalization. This increasing hyperintensity in DWIs were in agreement with the degree of histopathology during CPSE.nnnSUMMARYnThis study suggests that DWI is a useful imaging method for finding the epileptic focus or for examining potential epileptic brain damage in status epilepticus.

Combination therapy with transductive anti‐death FNK protein and FK506 ameliorates brain damage with focal transient ischemia in rat

Many practical therapies have been explored as clinical applications for ischemic cerebral infarction; however, most are still insufficient to treat acute stroke. We show here a potential combination therapy in a rat focal ischemic model to improve neurological symptoms as well as to reduce infarct volumes at the maximum level. We applied protein transduction technology using artificial anti‐death Bcl‐xl derivative with three amino acid‐substitutions (Y22F, Q26N and R165K) (FNK) protein fused with a protein‐transduction‐domain peptide (PTD‐FNK). When PTD‐FNK was administrated 1u2003h after initiating ischemia followed by the administration of an immunosuppressant FK506 with a 30‐min time lag, infarct volumes of the total brain and cortex were markedly reduced to 27% and 14%, respectively. This procedure not only reduced the infarct volume and edema, but also markedly improved neurological symptoms. The therapeutic effect continued for at least 1u2003week after ischemia. FK506 inhibited the transduction of PTD‐FNK in vitro, which explains the requirement of a time lag for the administration of FK506. An additional in vitro experiment showed that PTD‐FNK, when administered 30u2003min before FK506, gave the maximal protective effect by reducing the intracellular calcium concentration. We propose that this combination therapy would provide a synergistic protective effect by both drugs, reducing adverse the effects of FK506.

Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging.

The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction.

The effect of ozagrel sodium on photochemical thrombosis in rat: Therapeutic window and combined therapy with heparin sodium

The therapeutic efficacy of ozagrel sodium (ozagrel), alone and in combination with heparin, and its therapeutic time window were studied in a photochemically induced thrombotic cerebral infarction rat model. Cerebral artery thrombosis was induced by irradiating the brain with green light through intact skull using rose bengal as the photosensitizing dye. One set of animals was treated immediately after thrombosis with (1) vehicle, (2) 10 mg/kg ozagrel in saline, intravenously (i.v.), (3) 150 U/kg unfractioned heparin, subcutaneously (s.c.), or (4) ozagrel, i.v. plus heparin, s.c. Infarct volume was significantly smaller and edema was reduced in the ozagrel-treated groups compared to the vehicle-treated group; heparin did not convey additional benefit. In another set of animals, rats were given either vehicle or 10 mg/kg ozagrel in saline, i.v., 60 min or 120 min after induction of thrombosis. Ozagrel reduced infarct volume, but its effect diminished with delayed administration. The therapeutic window was determined to be less than 60 minutes after induction of thrombosis.

Clinical imaging diagnosis of implant materials for breast augmentation.

Background:The ingredients of substances implanted for breast augmentation sometimes remain unknown due to lack of information from patients. Significant clinical problems sometimes necessitate removal and reconstruction. Thus, preoperative diagnostic imaging to identify the ingredients of implants may improve the treatment decision-making process. In this report, we created a clinical imaging index. Purpose:Here, we summarize computed tomography (CT) and magnetic resonance imaging (MRI) imaging of implant materials to predict the ingredients of implant substances preoperatively. Methods:A total of 104 patients with late complications after receiving breast augmentations between 1971 and 2002 were examined using CT and MRI. In addition, further examinations were conducted, including postoperative chemical analysis using Nuclear magnetic resonance (NMR) spectroscopy and MRI imaging of various implanted substances using an experimental magnetic resonance system. Results:We identified the ingredients of implant materials used for breast augmentation by imaging diagnostics as follows: silicone: radiopaque-low/high (CT-MRI T1/T2); hydrogel: radiolucent-low∼iso/high; hydrocarbon: radiolucent-high∼iso/low∼iso; saline: radiolucent-low/high. Conclusion:We have identified by imaging diagnosis the ingredients of implant materials.

Aldose reductase and sorbitol dehydrogenase activities in diabetic brain: In vivo kinetic studies using 19F 3-FDG NMR in rats

The effects of diabetes mellitus on the kinetic constants of aldose reductase and sorbitol dehydrogenase in rat brain were investigated non-invasively in vivo using the 3-fluoro-3-deoxy-D-glucose (3-FDG) 19-fluorine (19F) nuclear magnetic resonance (NMR) method. While forward flux for both aldose reductase and sorbitol dehydrogenase (k1 and k2) were significantly increased, there was no corresponding increase in reverse flux (k1 and k2), and leakage of fructose (k5) was negligible. These findings indicate that the enzymatic kinetics of aldose reductase sorbitol (ARS) in diabetic brain undergo alteration favoring intracellular sorbitol and fructose accumulation, the frequently implicated biochemical basis of diabetic complications.

Therapeutic time window of rt-PA on embolic stroke in rat

Abstract rt-PA improves neurological outcome if it is administered at early time of stroke, and intracerebral hemorrhage is the main complication of thrombolytic therapy and it proves sometimes fatal. The aims of this study are to clarify the correlation between the efficacy of rt-PA, the severity of hemorrhage and treatment delay, using the developed embolic infarction model. Fibrin-rich clots were used to occlude MCA on Sprague–Dawley rats. Alteplase of 10 mg/kg was administrated via femoral vein at 30 (n=7), 60 (n=10), 90 (n=6) and 120 (n=6) min after clot embolization and vehicle group (n=10) received saline. Twenty four hours after embolization, brains were perfused with PBS and TTC stain was utilized to measure the infarct volume. Hemorrhage volume was quantified with spectrophotometric assay of extraction from ischemic hemisphere. Infarction was significantly smaller in the groups administrated altepalse at 30, 60 and 90 min and hemorrhage was significantly less in the group of 30 min than vehicle group. However, administration of alteplase at 120 min did not ameliorate infarction and more significantly increased hemorrhage than vehicle group. In these results, we clearly showed that vascular therapeutic time window of this model can be within 120 min and treatment delay of thrombolysis enhanced the severity of hemorrhagic transformation.

Cerebral blood flow index image as a simple indicator for the fate of acute ischemic lesion

BACKGROUND AND PURPOSEnTo evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, we attempted to investigate 1) whether CBF index images can reveal the resulting infracted area, 2) whether the CBF index can correlate other modality (SPECT).nnnMETHODSnDWI and DPI were obtained in 17 patients within 12 hours of stroke onset and follow up MRI. On three DPI delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, correlations between initial lesion volume of and follow up infarction volume of three images and rCBF images delivered with singular value decomposition (SVD) methods were assessed. Then 99mTc-ECD SPECT was taken immediately after MRI to correlate to MRI data.nnnRESULTSnAmong the three images, lesion volume of CBF index images against follow up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) and had identical accuracy to the regression coefficient of rCBF images. CBF index well correlated to SPECT delivered CBF.nnnCONCLUSIONnCBF index images can accurately predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

Effect of a New Calcium Antagonist (SM-6586) on Experimental Cerebral Ischemia

SM-6586 (SM) is a new derivative of dihydropyridine with potent calcium blocking activity and inhibitory activity of the Na+/H+ and Na+/Ca++ exchange transport. The effect of SM on survival rate, brain edema and metabolites was evaluated using two different models in spontaneously hypertensive rat (SHR). Global ischemia was induced by bilateral common carotid artery ligation (BLCL) and focal ischemia was induced by middle cerebral artery occlusion. The survival rate after BLCL was higher in the SM-treated group. The brain water content was lower, the ATP level was higher and lactate level was lower in the SM-treated group compared to the control group. In focal ischemia models, the SM-treated group showed a reduction of T1 relaxation time. The brain water content was significantly decreased in the SM-treated group. These results indicate that SM was effective in ameliorating the ischemic insult in global and focal cerebral ischemia models.

Transient disappearance of white matter lesions on correction of hyponatremia

The nature of white matter lesions (WMLs), commonly seen on MRI in the elderly, is controversial. We describe a rare phenomenon of transient disappearance of WMLs during correction of hyponatremia.