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

Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning

Long-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected. We found that fiberoptic illumination to Purkinje cells expressing PhotonSABER in vivo inhibited cerebellar motor learning during adaptation of the horizontal optokinetic response and vestibulo-ocular reflex, as well as synaptic AMPA receptor decrease in the flocculus. Our results demonstrate that LTD and AMPA receptor endocytosis at specific neuronal circuits were directly responsible for motor learning in vivo

Bony Landmarks of the Anterior Cruciate Ligament Tibial Footprint

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

<i>Propionibacterium acnes</i>-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis

<div><p>Background</p><p><i>Propionibacterium acnes</i> is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect <i>P</i>. <i>acnes</i>-derived immune complexes in sarcoid lesions.</p><p>Methods</p><p>We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a <i>P</i>. <i>acnes</i>-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of <i>P</i>. <i>acnes</i>.</p><p>Results</p><p>Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming <i>P</i>. <i>acnes</i>). MT treatment revealed abundant IIC-forming <i>P</i>. <i>acnes</i> in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming <i>P</i>. <i>acnes</i> was detected in control samples without inflammation. IIC-forming <i>P</i>. <i>acnes</i> were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming <i>P</i>. <i>acnes</i>. Conventional electron microscopy identified many SRBs (0.5–2.0 μm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming <i>P</i>. <i>acnes</i>, some of which were in phagolysosomes with a degraded and lamellar appearance.</p><p>Conclusions</p><p><i>P</i>. <i>acnes</i>-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.</p></div

Frequency of PAB-reactive granuloma cells, HW-bodies, and SRBs in sarcoid and control lymph nodes.

<p>Frequency of PAB-reactive granuloma cells, HW-bodies, and SRBs in sarcoid and control lymph nodes.</p