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Background: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. Objective: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. Materials and methods: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL-rats was used as an index. Results: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle-rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL-rats. Conclusion: There findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.

早大学位記番号:新8539

The present study aimed to specify the cerebral sulci developed by cortical expansion in cynomolgus monkey fetuses. The degree of sulcal infolding was evaluated by the gyrification index (GI), which was quantified using ex vivo MRI. The correlation of cortical volume with the sulcal GI was most frequent during embryonic days (EDs) 100 to 120. Interestingly, the high correlation was marked during EDs 140 to 150 in restricted primary sulci in prefrontal, parietotemporal and medial temporal regions. The present results suggest that cortical expansion is involved in gyral demarcation by sulcal infolding, followed by the sulcal infolding progression in phylogenetically-newer cortices.

To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6 to 10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects.Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence, would be useful to examine the effects of valproic acid on somitogenesis and morphogenesis of somite-associated structures.

Screw malposition, such as lateral wall breach or end-plate breach, is one of the main pitfalls of inserting pedicle screws. Methods: From 17 fresh spines 54 vertebrae were harvested. In each vertebra on one pedicle the screw was inserted correctly down the axis of the pedicle, while on the other pedicle the screw was inserted to breach the lateral wall or the end-plate. The 18 pedicle screws that breached the lateral wall were then removed and re-directed along the correct axis of the pedicle. The 18 pedicle screws that breached the end-plate were removed and re-directed along the correct axis of the pedicle. The 18 other pedicle screws that had breached the end-plate were not removed. The pullout force of pedicle screws was measured. Results: 1) The mean pullout strength for the re-directed screws following lateral wall breach was 24.0% less as compared to the correctly aligned screws; 2) The mean pullout strength for the re-directed screws following end-plate breach was 23.3% less as compared to the correctly aligned screws; 3) The mean pullout strength for the pedicle screws end-plate breach was 7.6% less as compared to the correctly aligned screws. Conclusion: The pullout strength of re-directed pedicle screws after either a lateral pedicle breach or end-plate breach is significantly less than the pullout strength of correctly aligned screw. A pedicle screw that is not re-directed after end-plate breach is weaker than a pedicle screw correctly aligned, however the difference is not significant.

Study Design. Using fresh cadavers, real-time dosimeters were used to estimate the radiation exposure dose from C-arm fluoroscopy to surgeons, medical staff, and patients during various procedures. Objective. To evaluate the radiation exposure dose from C-arm fluoroscopy, which is used to generate real-time images of the human body, under a variety of conditions and in different areas. Summary of Background Data. Awareness of the harmful effects of long-term low-dose radiation is rising. There are no all-inclusive reports evaluating the radiation exposure dose to medical staff associated with fluoroscopic procedures which can accurately simulate the real clinical situation. Methods. Seven fresh cadavers were irradiated for 1, 3, and 5 min with C-arm fluoroscopy. The X-ray source was positioned under the table, over the table, and laterally. Radiation exposure doses were measured at different simulated areas such as the center area, and the surgeon’s hand or thyroid gland. Results. There were significant differences in the radiation exposure dose under different conditions and for different irradiated areas. The risk of direct and scatter radiation exposure was the greatest with the lateral position, which increased by more than 200 times and more than 30 times, respectively, compared with that from a position under the table. Direct radiation was attenuated to less than one-hundredth after passing through the body of the cadaver. All radiation exposure doses were positively correlated with total exposure time. Conclusions. Our study revealed the direct and scatter radiation exposure dose from C-arm fluoroscopy to different areas under a variety of conditions when fluoroscopy is used to generate real-time images of the human body. Our results serve as a guide for medical staff to understand the risk of radiation exposure during each fluoroscopic procedure. Medical staff, especially surgeons, should consider how to protect themselves and reduce radiation exposure by using appropriate shielding.

Background: Previous studies suggested that changes in kinematics in total knee arthroplasty (TKA) affected satisfaction level. The aim of this cadaveric study was to evaluate the effect of medial collateral ligament (MCL) release by multiple needle puncture on knee rotational kinematics in posterior-stabilized TKA. Methods: Six fresh, frozen cadaveric knees were included in this study. All TKA procedures were performed with an image-free navigation system using a 10-mm polyethylene insert. Tibial internal rotation was assessed to evaluate intraoperative knee kinematics. Multiple needle puncturing was performed 5,10, and 15 times for the hard portion of the MCL at 90° knee flexion. Kinematic analysis was performed after every 5 punctures. After performing 15 punctures, a 14-mm polyethylene insert was inserted, and kinematic analysis was performed. Results: The tibial internal rotation angle at maximum knee flexion without multiple needle puncturing was significantly larger (9.42°) than that after 15 punctures (3°). Negative correlation (Pearson r.＝0.715, P < .001) between tibial internal rotation angle at maximum knee flexion and frequency of puncture was observed. The tibial internal rotation angle with a 14-mm insert was significantly larger (7.25°) compared with the angle after 15 punctures. Conclusion: Tibial internal rotation during knee flexion was reduced by extensive MCL release using multiple needle puncturing and was recovered by increasing of medial tightness. From the point of view of knee kinematics, medial tightness should be allowed to maintain the internal rotation angle of the tibia during knee flexion which might lead to patient satisfaction.

Prenatal ethanol exposure causes the reduction of serotonergic (5-HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5-HT2A and 5-HT2C receptors during the fetal period is able to prevent the reduction of 5-HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague-Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair-fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist for 5-HT2A/2C receptors, during GDs 13 to 19 (Et-DOI or Pf-DOI), and another was injected with saline vehicle only (Et-Sal or Pf-Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5-HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5-HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et-Sal fetuses compared to that of the Pf-Sal and Pf-DOI fetuses, whereas there were no significant differences between Et-DOI and each Pf control. Thus, we concluded that the reduction of 5-HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5-HT2A/2C receptors during the fetal period.

The purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. The monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. The fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. Consistently, lengths of the major primary sulci reached adult levels by 3 months of age, and then decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry quotient analysis showed that sulcal length asymmetry patterns gradually changed during postnatal development. The male adult pattern of sulcal length asymmetry was acquired after 24 months of age. In particular, age-dependent rightward lateralization of the arcuate sulcal length was revealed during cerebral maturation by three-way ANOVA. The results suggest that the regional difference in cerebral maturation from adolescence to young adulthood modifies the sulcal morphology with characteristic asymmetric patterns in male cynomolgus monkeys.

Diffusion tensor imaging (DTI) was conducted on the fixed brains of cynomolgus monkey fetuses at embryonic days (EDs) 70-140. DTI color maps revealed the commissural tracts such as the corpus callosum and anterior commissure, and the projection tracts such as the internal capsules, coronal and optic radiations, and the limbic tracts such as the cingulum and fornix, already forming on ED 70. The corpus callosum grew into the occipital subcortical region between the optic radiation and the medial cortical surface when the calcarine sulcus began to indent on ED 80. The corticocortical long associative fibers became distinguishable sequentially with the stages in the development of the fetuses, and the emergence of those fibers was spatiotemporally related to the emergence of other primary sulci. The unicinate fibers were observed along the indentation of the lateral fissure rostrocaudally on ED 70, while the inferior longitudinal fasciculus emerged corresponding to the emergence of the superior temporal sulcus on ED 80 and the emergence of the lunate sulcus on ED 120; the superior longitudinal fasciculus appeared throughout the frontoparietal region, corresponding to the emergence of parietooccipital sulcus on ED 80 and the emergence of the arcuate and central sulci on ED 90. Furthermore, some but not all cortical convolutions were formed at the gap of two association fiber tracts. For example, the convolution of the superior temporal gyrus at the gap between the unicinate and inferior longitudinal fascicule, and the convolution of the inferior temporal gyrus at the gap between the inferior and superior longitudinal fascicule were observed. These results suggest that the emerging corticocortical long associative fibers link spatiotemporally with the formation of primary sulci in the cynomolgus monkey cerebrum.

In the present study developmental changes in the cerebral sulci and volumes of subcortical and archicortical structures of the cerebrum in cynomolgus monkey fetuses were examined with T(1)-weighted magnetic resonance (MR) images in 3D. On the embryonic day (ED) 90, the lateral ventricle had still an immature vesicular shape in the occipital region of the cerebrum, and it dramatically closed its lumen by ED 100. In that period the calcarine sulcus progressively infolded from the medial surface of the cerebral hemisphere narrowing the lumen of the lateral ventricle in the occipital region. Volume of the lateral ventricle decreased in the period ED 90-100, increasing afterwards in spite of increasing volumes of subcortical and archicortical structures such as the caudate nucleus, putamen, globus pallidus, amygdala and hippocampal formation. During the same time, the volume of the germinal matrix around lateral ventricles decreased to disappear completely by ED 120. These results suggest that the morphological maturation of lateral ventricle is linked to the development of calcarine sulcus in cynomolgus monkey fetuses. The degree of infolding of calcarine sulcus on ED 100 would be useful as a gross anatomical landmark for evaluating the cerebral maturation in cynomolgus monkey fetuses.