Ichiro Shimoyama

Relation between protein kinase C and calmodulin systems in cerebrovascular contraction: investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage.

The protein kinase C (PKC) and calmodulin systems each play a role in vascular contraction. However, the correlation of these two systems in producing contraction has been unclear. To clarify the pathophysiology of vasospasm after subarachnoid hemorrhage, the authors demonstrated tonic contraction of the cerebral artery in a study of isometric tension, and investigated the correlation of the PKC and calmodulin systems in producing the contraction. To develop better management for vasospasm, they also examined the effect of calmodulin antagonists on tonic contraction. The development of isometric tension in canine basilar arteries was measured, with the following results: 1) tonic contraction was dependent on the PKC system, but initiation of the contraction by the calmodulin system was necessary for the subsequent PKC-dependent tonic contraction; 2) specific calmodulin antagonists like chlorpromazine and pimozide partially inhibited the tonic contraction associated with PKC activation; 3) another calmodulin antagonist, trifluoperazine, inhibited the PKC system as well. On the basis of these results, the authors conclude that the PKC system plays a role in the development of vasospasm. In the early phase of contraction, the calmodulin system contributes to the subsequent fully-activated, PKC-induced tonic contraction. To manage vasospasm, a specific calmodulin antagonist would therefore not be sufficient. Suppression of both the calmodulin and PKC systems with trifluoperazine in the earliest stage of vasospasm is recommended.

Therapeutic Effect of a New Immunosuppressant, FK-506, on Vasospasm after Subarachnoid Hemorrhage

We hypothesized that the immunological reaction against extravasated blood might play a role in the development of vasospasm after subarachnoid hemorrhage. Under the hypothesis, we had reported significant therapeutic efficacy of cyclosporin A on vasospasm in canine models. We here investigated the efficacy of a new, potent immunosuppressant, FK-506, on vasospasm in animal models. Dogs were randomly classified into sham operated, subarachnoid hemorrhage treated-1 group, (FK-506, 0.3 mg/kg-d, intramuscular injection), and treated-2 group (FK-506, 0.15 mg/kg-d, intramuscular injection). Levels of the third factor of complement (C3) and the activity of serum complement inducing 50% hemolysis of sheep erythrocytes (CH50) in serum were also determined. In the treated groups, the levels of FK-506 in serum were monitored. As for C3 and CH50, there were no statistically significant differences among the groups and there were no changes between Day 1 and Day 7 in any group. Angiographical diameters of a basilar artery on Days 1 and 7 were measured with a computed image analyzer, and the extent of vasospasm was compared among the groups. Statistically significant differences between the sham-operated group and the other three groups were noted. However, under sufficient levels of FK-506 in serum, the extent of vasospasm in either treated group was the same as that in the subarachnoid hemorrhage group. These results indicate a significant discrepancy in the therapeutic mechanism for vasospasm between cyclosporin A and FK-506. They have common aspects in the immunosuppressive mechanism. However, in T-cell suppression, the different mechanism in situ between the two drugs is also postulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Verbal versus non-verbal visual evoked potentials: Kanji versus line drawings.

SummaryCortical areas related to perception of verbal and non-verbal stimuli were studied using VEPs. Kanji characters, line drawings (LD), or a blank were displayed. Verbal VEPs were obtained by subtracting the blank-VEPs from the Kanji-VEPs, and non-verbal VEPs by subtracting the blank-VEPs from the LD-VEPs. Both the verbal and non-verbal VEPs showed a negative peak (100–300 msec) focally over bilateral occipital, posterior temporal and parietal areas, and a positive peak diffusely over frontal halves. Difference between the non-verbal from the verbal VEPs showed an initial peak (100–200 msec) focally over bilateral occipital and posterior temporal areas, followed by a peak (200–300 msec) focally over bilateral posterior temporal areas. The frontal areas diffusely showed peaks at 100–200, 200–300 and 300–400 msec. Left-right asymmetries of both the verbal and non-verbal VEPs showed peaks between 100 and 300 msec over posterior temporal, parietal, and occipital areas. Left-right asymmetries of the subtraction to the non-verbal from the verbal VEPs showed a peak (100 msec) over occipital and parietal areas, and a broader peak over posterior temporal area (100–200 msec). Bilateral occipital, posterior temporal, and parietal areas are focally activated by the two perceptions (100–300 msec), while frontal areas are activated diffusely. Further, different processes may be focally involved between the hemispheres over occipital (100–200 msec) and posterior temporal (100–200 and 200–300 msec) regions. Initial left-right asymmetries of the subtracted VEP between the two perception would occur over occipital and parietal areas (100 msec) and last for 200 msec over posterior temporal area.

Eclampsia-like seizures and electroencephalographic changes in pregnant rabbits with endothelin-1 injections

To examine the possible role of endothelin and vasospasm in eclamptic seizures, we studied and analyzed the electroencephalograms (EEG) of endothelin-1 (ET-1)-treated pregnant, nonpregnant and sham control (dextrose-treated) rabbits. After multiple intravenous bolus injections of ET-1 (500 pmol/kg) or 5% dextrose in the rabbits, we recorded EEG directly from the brain cortex and analyzed by Fast Fourier Transform (FFT). Water content was measured in the brain of all groups (n = 7). Repeated seizures occurred in all of the pregnant and 2 of the nonpregnant rabbits by variable doses of ET-1. FFT analysis showed remarkable changes in frequency and power arrays characterized by mild to severe form of dysrhythmia, high-voltage spikes, high-voltage fast and slow waves after ET-1 injections. Water content was increased in brain mass in ET-1-treated rabbits (p = 0.001) suggesting an ET-1-induced edema. Histologically we confirmed that ET-1 caused ischemic changes in brain tissues. However, ET-1 induced more pronounced changes in behavior, EEG, brain edema or ischemia in pregnant than in nonpregnant groups. The injections of exogenous ET-1 into the brain substances were strongly suggested by immunohistochemical study with polyclonal antiendothelin antibody in brain tissue sections. Therefore, we assume that endothelin along with other vasoactive substances causes acute cerebral vasospasm and ischemia inducing EEG changes leading to ultimate clinical convulsions in eclampsia.

Intraoperative Facial Nerve Monitoring by Monopolar Low Constant Current Stimulation and Postoperative Facial Function in Acoustic Tumor Surgery

Among the several methods of intraoperative facial nerve monitoring in acoustic neurinoma surgery, the evoked facial muscle responses (EFMR) by electrical stimulation of the nerve have been most commonly and effectively used [2, 4]. However, the most effective stimulus parameters during surgery have not yet been defined. In the past 9 years, monopolar low constant current stimulation (0.5–0.6 nA) was applied in 52 cases. We report intraoperative findings of the EFMR and their relations to postoperative facial functions.

LINE-DRAWING TEST ACROSS AGES '"

A line-drawing test was standardized for normal subjects to examine effects of normal aging. For this purpose, the results of the test for 168 normal volunteers were quantified using a digitizer and a microcomputer across ages from 9 to 78 yr. Three sets of parallel vertical lines were presented to every subject, the distances between the parallel vertical lines (5. 10, and 15 cm) differed in the three sets. A subject drew an horizontal line starting exactly on the left vertical line and stopped exactly on the right one, and the computer could detect minute inaccuracy at the start and at the stop, which inaccuracy was expressed in mm. In this study, effects of four parameters were evaluated, i.e., ages, sex, distances from the paired vertical lines, and order of trials; all were nonsignificant. The normal range of the deviations was within 2.1 mm (average + 2 SD).

Experimental Study of the Correlation Between Evoked Potentials (SEP and AEP) and the Perfusion Pressure

Inflating a balloon in the supratentorial epidural space (Nagao et al. 1979; Tsutsui et al. 1986) and infusing solutions (Foltz et al. 1987) into the lateral ventricle have been used to study increased intracranial pressure (ICP) experimentally. However, the balloon technique is not biological because the inflated balloon itself could damage the underlying cerebral cortex. We developed a new technique for production of increased ICP to overcome this problem.

Statistical analysis of short-latency flash visual evoked cortical potentials with noncephalic reference

Most of the reports on visual evoked cortical potentials have dealt with peak latency or amplitude. An early negative deflection at about 20 ms, however, was reported to coincide with the initial signal to the monkey cortex. We studied the initial signal to the human cortex in nine volunteers by taking into account prestimulus fluctuation. Visual evoked cortical potentials were recorded for an interval 10 ms before and 92.4 ms, after a flash stimulus, by means of a neck reference. The amplitudes of the response before the flash stimulus and at each succeeding 5-ms interval after the stimulus were tested with at-test. The grand average of the visual evoked cortical potentials showed an initial negative peak at 22.3 ms over the frontal poles, a second negative peak at 52.4 ms over the central area, and a third negative peak at 74.7 ms over the occipital areas. The topographic maps corresponding to the peaks of the visual evoked cortical potentials were the same as those of the dynamict-values. The visual evoked cortical potential andt-values with the bipolar and source derivations showed a marked response beginning around 40 ms over the posterior head. This statistical analysis is an easy method to standardize evoked potentials and to identify deflections.