Acetyl-L-carnitine enhances myelination of regenerated fibers of the lateral olfactory tract

It is well known that acetyl-L-carnitine (ALC) has various neuroprotective effects against neurodegenerative diseases. In addition, it has been reported that ALC facilitates myelination of regenerated axons after peripheral nerve injuries. We previously reported that spontaneous regeneration of the lateral olfactory tract (LOT), the main fiber tract of the central olfactory system, consistently occurred in newborn rats and a majority of these regenerated fibers were unmyelinated in neonatally LOT-transected young adult rats. To investigate the effects of ALC treatment on myelination in LOT, neonatal rats were treated with ALC after LOT transection. Immunohistochemistry for myelin basic protein showed more positive areas in ALC-treated rats than in control rats. Moreover, the number of myelinated axons of regenerated fibers was assessed using electron microscopy and was found to be statistically higher in ALC-treated rats compared to control rats. The study revealed that ALC accelerates myelination of regenerated fibers in neonatally LOT-injured young adult rats. (C) 2017 Elsevier B.V. All rights reserved.ArticleNEUROSCIENCE LETTERS.653:215-219(2017)journal articl

Functional correlation between olfaction and various sectioning of the lateral olfactory tract

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第915号）・関口泰之The lateral olfactory tract (LOT) is a central olfactory pathway, and efferent projections from the olfactory bulb are conveyed to the olfactory-related cortical structures via the LOT. The purpose of the present study is to determine the exact site of the LOT causing functional impairment in animals. After ablation of the right olfactory bulb, rats received rostrocaudal transection injuries on the left LOT at different levels between the olfactory bulb and the middle cerebral artery. Olfactory function of LOT-transected rats was studied by examining their olfactory ability to discriminate between the smell of water and cycloheximide solution, a strong repellent for rodents. Rats were divided into two groups based on their olfactory discriminative abilities. The olfaction positive (+) group achieved 83% +/- 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery of this group ranged between 0.8 and 2.4 mm (n = 8). The olfaction negative (-) group achieved 48% +/- 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery ranged between 2.5 and 4.2 mm (n = 10). From these data, we concluded that the site of the LOT critical for olfactory function is located approximately 2.5 mm from the middle cerebral artery. (c) 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.ArticleNEUROSCIENCE RESEARCH. 73(1):17-23 (2012)journal articl

Analysis of spontaneous regeneration of olfactory structures with emphasis on myelination and re-innervation of cortical areas

Regeneration of the lateral olfactory tract (LOT) occurs spontaneously after transection in developing rats. In neonatally LOT-transected rats, we observed a newly formed myelinated tract near the rhinal sulcus. The aim of this study was to analyze the precise re-innervated cortical areas and to demonstrate ectopic LOT myelination in neonatally LOT-transected rats. Neonatal rats were subjected to unilateral LOT transection and simultaneous injection of a retrograde fluorescent tracer into the posterior olfactory cortex to evaluate the degree of transection. After 8 weeks, bilateral olfactory bulbs of the rats were subjected to multiple injections of an anterograde neuronal tracer to determine the extent of the regenerated fibers. In the completely LOT-transected rats, the regenerated fibers were distributed in the anterior olfactory cortices: the anterior olfactory nucleus, the olfactory tubercle, and the rostral part of the piriform cortex. Ectopic myelination of LOT was evident immediately below the rhinal sulcus in the completely and incompletely LOT-transected rats. We concluded that the regenerated bulbar fibers were confined to the regions of the anterior olfactory cortices and that ectopic myelination of the regenerated LOT occurred only at a specific site near the rhinal sulcus.ArticleNEUROSCIENCE LETTERS. 537:35-39 (2013)journal articl

Effects of repeated crush injuries on motor functional recovery of the sciatic nerve

信州大学博士（医学）・学位論文・平成25年1月30日授与（乙第1153号）・伊坪 敏郎Objectives: The present study was conducted to examine whether repeated crush injuries have significant effects on motor functional recovery of peripheral nerves. Methods: Repeated crush injuries of the sciatic nerve were inflicted on adult rats at 1-week intervals, and functionality of the sciatic nerve was assessed by the static sciatic index each week for 8 weeks after the final injury. To determine the effects of repeated crush injuries on motor functional recovery of the sciatic nerve, tibialis anterior muscle fibers from single and triple crush injuries were examined, and fiber size and fiber reinnervation during the 2- to 4-week period after the final injury were measured. Results: Compared to single crush injuries, which completely recovered by post-injury week 4, double crush injuries resulted in retarded, but complete recovery by post-injury week 6, whereas triple crush injuries resulted in marked retardation in the regenerative process with incomplete recovery during week 8 of the experimental period. Muscle fiber size for rats with triple crush did not recover to normal range at post-injury week 4, despite its normal size for rats with single crush. The rate of reinnervation increased prominently between post-injury weeks 2 and 3 in both injuries, but the rate with triple crush was lower than that with single crush at post-injury week 3. Discussion: These results, which contradict those of a previous study that reported early functional recovery, indicate that repeated crush injuries inhibit motor functional recovery of the damaged sciatic nerve, as evidenced by delayed and incomplete regeneration, atrophied muscle fibers, and delayed reinnervation.ArticleNEUROLOGICAL RESEARCH. 34(9):908-914 (2012)journal articl

Bony Landmarks of the Anterior Cruciate Ligament Tibial Footprint A Detailed Analysis Comparing 3-Dimensional Computed Tomography Images to Visual and Histological Evaluations

Background: Although the importance of tibial tunnel position for achieving stability after anterior cruciate ligament (ACL) reconstruction was recently recognized, there are fewer detailed reports of the anatomy of the tibial topographic footprint compared with the femoral side. Hypothesis: The ACL tibial footprint has a relationship to bony prominences and surrounding bony landmarks. Study Design: Descriptive laboratory study. Methods: This study consisted of 2 anatomic procedures for the identification of bony prominences that correspond to the ACL tibial footprint and 3 surrounding landmarks: the anterior ridge, lateral groove, and intertubercular fossa. In the first procedure, after computed tomography (CT) was performed on 12 paired, embalmed cadaveric knees, 12 knees were visually observed, while their contralateral knees were histologically observed. Comparisons were made between macroscopic and microscopic findings and 3-dimensional (3D) CT images of these bony landmarks. In the second procedure, the shape of the bony prominence and incidence of their bony landmarks were evaluated from the preoperative CT data of 60 knee joints. Results: In the first procedure, we were able to confirm a bony prominence and all 3 surrounding landmarks by CT in all cases. Visual evaluation confirmed a small bony eminence at the anterior boundary of the ACL. The lateral groove was not confirmed macroscopically. The ACL was not attached to the lateral intercondylar tubercle, ACL tibial ridge, and intertubercular space at the posterior boundary. Histological evaluation confirmed that the anterior ridge and lateral groove were positioned at the anterior and lateral boundaries, respectively. There was no ligament tissue on the intercondylar space corresponding to the intercondylar fossa. In the second investigation, the bony prominence showed 2 morphological patterns: an oval type (58.3%) and a triangular type (41.6%). The 3 bony landmarks, including the anterior ridge, lateral groove, and intertubercular fossa, existed in 96.6%, 100.0%, and 96.6% of the cases, respectively. Conclusion: There is a bony prominence corresponding to the ACL footprint and bony landmarks on the anterior, posterior, and lateral boundaries.ArticleAMERICAN JOURNAL OF SPORTS MEDICINE. 42(6):1433-1440 (2014)journal articl

Actin-Independent Behavior and Membrane Deformation Exhibited by the Four-Transmembrane Protein M6a

M6a is a four-transmembrane protein that is abundantly expressed in the nervous system. Previous studies have shown that over-expression of this protein induces various cellular protrusions, such as neurites, filopodia, and dendritic spines. In this detailed characterization of M6a-induced structures, we found their varied and peculiar characteristics. Notably, the M6ainduced protrusions were mostly devoid of actin filaments or microtubules and exhibited free random vibrating motion. Moreover, when an antibody bound to M6a, the membrane-wrapped protrusions were suddenly disrupted, leading to perturbation of the surrounding membrane dynamics involving phosphoinositide signaling. During single-molecule analysis, M6a exhibited cytoskeleton-independent movement and became selectively entrapped along the cell perimeter in an actin-independent manner. These observations highlight the unusual characteristics of M6a, which may have